In Vivo Metabolic Disease

The in vivo department offers a wide variety of established and validated models in the area of metabolic diseases (Diabetes Type 1 and 2, Liver fibrosis, -steatosis and MASH). All our models hit high quality standards. Flexible study designs and custom designed studies can be discussed. Due to Evotec´s capabilities, an extensive number of readouts can be evaluated in house featuring relevant clinical readouts, single cell analysis and omics. Our scientists hold outstanding expertise in executing in vivo studies in drug discovery. We offer consultation, support and conduction of in vivo studies with high quality output.

We offer the option of pre feeding animals in-house to provide cohorts of animals with diet-induced obesity. Quality controls ensure that only responders are transferred to the follow up studies.

Model of Diet-induced Obesity (DIO)

• Highly translatable model for obesity/metabolic syndrome studies
• Non-responder identified and excluded
• Body composition monitoring
• Development of adiposity and diabetes
• Standard of care benchmark available

The db/db mouse is a robust and highly translatable model of early and established Type 2 diabetes.

Model of Diabetes Type 2 (Db/Db mice)

• Insulin resistance, obesity and hyperglycemia/ diabetes
• Mutation in leptin receptor leads to disruption of satiety signaling
• Body composition monitoring
• Defined age of onset facilitates studies in pre-diabetic or diabetic animals
• Standard of care benchmark available

We offer animal models for hepatic steatosis based on differently composed high fat diets.

Model of Diet-induced Hepatic Steatosis

• Different high fat diet-induced hepatic steatosis models available with flexible treatment time
• Adaptable for PD and efficacy utilization
• Prevention and intervention set-ups available

This model allows compound testing in the field of MASLD/MASH with mild fibrosis. The phenotype is induced by feeding C57BL/6 animals high fat (40 kcal%), high fructose (20 %), high cholesterol (2 %) diet.

Model of Diet-induced MASH with Mild Liver Fibrosis

• Very well translatable efficacy MASH model with severe hepatic macrovesicular steatosis, mild-to-moderate hepatic inflammation and mild liver fibrosis after 20 weeks of diet
• Development of mild obesity and glucose intolerance
• Intervention set-up

This model allows compound testing in the field of MASLD/MASH with moderate fibrosis. 

ob/ob mice are characterized by severe obesity with transient hyperglycemia and hepatic steatosis. Feeding a high fat (40 kcal%), high fructose (20 %), high cholesterol (2 %) diet further induces hepatic inflammation and liver fibrosis.

Model of Diet-induced MASH with Moderate Liver Fibrosis in ob/ob Mice

• Well translatable efficacy model with progressive MASH phenotype, moderate liver fibrosis and severe obese phenotype
• In contrast to C57BL/6 mice, ob/ob show an accelerated phenotype
• Intervention set-up

This model allows the rapid evaluation of compounds acting on liver fibrosis. Anti-fibrotic effects of compounds can be studied independently of metabolic effects.

Model for Advanced Liver Fibrosis

• Robust and well reproducible development of liver fibrosis within 2 weeks of carbon tetrachloride (CCl₄) injection
• Screening of compounds in a prevention (2 weeks) or intervention (4 weeks) set-up

This model utilizes NOD/ShiLTJ mice and closely mimics the Type 1 diabetes phenotype.

Spontaneous Autoimmune T1D Model

• 50-90% of female mice develop spontaneous autoimmune diabetes between 10 and 30 weeks of age
• The dominant initial population consists of CD4+ T cells, followed by the infiltration of CD8+ T cells, macrophages, and B cells into smaller numbers

A model of Type 1 and 2 diabetes in which effective chemically induced degradation of pancreatic beta cells is achieved.

STZ Induced Diabetes

• Injection with one high or multiple low doses of streptozotocin (STZ) to destroy endogenous beta cells
• Can be used for compound treatment to reverse diabetes in immunocompetent animal
• Alternatively, immunodeficient animals are transplanted with human-derived islet-like clusters (ILCs) or cadaveric human islets under the kidney capsule

Monogenic model for phenotypes associated with Type 1 Diabetes e.g. ER stress or diabetic complications.

C57BL/6-Ins2Akita/J mice

• Spontaneous mutation in insulin 2 gene - incorrect folding of insulin protein
• Reduced insulin secretion, which is a consequence of reduced beta cell mass/beta cell toxicity
• Course of disease differs in male than in female mice